Tri-Leaflet Prosthetic Heart Valve

ABSTRACT

A prosthetic heart valve includes a first upper frame portion and a stent frame connected to the first upper frame portion via at least two stent frame extensions. The stent frame includes a base and at least two stent posts extending upwardly from the base towards the first upper frame portion. The first upper frame portion, the base, and the at least two stent posts each has an inner surface and an outer surface. The prosthetic heart valve also includes at least one sheet of leaflet material configured to encircle the stent frame and weave through the stent frame between the first upper frame portion and the base.

CROSS REFERENCE OF RELATED APPLICATION

This application claims the benefit of the U.S. Provisional PatentApplication No. 62/527,632 filed Jun. 30, 2017, which is incorporatedherein by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to the manufacture and use of a prostheticvalve for use in the human heart. More specifically, the inventionrelates to the manufacture and use of a valve that may be surgicallyimplanted into the heart of a patient in order to replace a nativetri-leaflet heart valve.

BACKGROUND

Heart valve replacement is the second most common cardiac operationperformed in the United States. Currently, over four million people arediagnosed with heart valve disorder across the world, each year.Moreover, heart disease is prevalent in about 2.5% of the overall UnitedStates population, and 10.4% of its elderly population.

Typically, prosthetic heart valves used in aortic and mitral heart valvereplacement procedures are either mechanical or bioprosthetic. However,these valves introduce significant risk of thromboembolism, requiringthe patient to undergo lifelong anticoagulation therapy, or the patientbecome more prone to valve degeneration and tissue failure, requiringreoperation. It would be useful to produce a prosthetic heart valve thatwould be durable, while not necessitating anticoagulation therapy.

SUMMARY

A prosthetic heart valve includes a first upper frame portion and astent frame connected to the first upper frame portion via at least twostent frame extensions. The stent frame includes a base and at least twostent posts extending upwardly from the base towards the first upperframe portion. The first upper frame portion, the base, and the at leasttwo stent posts each has an inner surface and an outer surface. Theprosthetic heart valve also includes at least one sheet of leafletmaterial configured to weave through the stent frame between the firstupper frame portion and the base.

A prosthetic heart valve includes a stent frame with a first upper frameportion, a base, and at least two stent posts extending upwardly fromthe base; wherein the base is connected to the first upper frame portionby the at least two stent posts, and wherein the first upper frameportion, the base, and the at least two stent posts each has an innersurface and an outer surface; and at least one sheet of leaflet materialconfigured to weave through the stent frame from the outer surface tothe inner surface between the first upper frame portion and the base ofthe stent frame.

In another embodiment, the at least one sheet of leaflet material isdisposed on the outer surface of the base and of the at least two stentposts, and at least a portion of the at least one sheet of leafletmaterial is tucked under the first upper frame portion between the firstupper frame portion and the base and is disposed on the inner surface ofthe upper frame portion.

In another embodiment, the at least one sheet of leaflet material isdisposed on the inner surface of the base and of the at least two stentposts, and at least a portion of the at least one sheet of leafletmaterial is tucked in under the first upper frame portion between thefirst upper frame portion and the base.

In another embodiment, the first upper frame portion has a shape that issubstantially similar to an upper edge of the base.

In another embodiment, the stent frame further comprises a second upperframe portion connected to the first upper frame portion, and whereinthe second upper frame portion has a shape that is substantially similarto an upper edge of the first upper frame portion. The stent frame mayalso include a third upper frame portion connected to the second upperframe portion, wherein the third upper frame portion has a shape that issubstantially similar to an upper edge of the second upper frameportion. Moreover, the at least one sheet of leaflet material weavesthrough the stent frame between the first upper frame portion and thesecond upper frame portion and/or between the second upper frame portionand the third upper frame portion.

The base may further have a lower edge that is substantially similar toa lower edge of the first upper frame portion. And, the at least twostent posts have at least two heights different from one another.

In one embodiment, the at least one sheet of leaflet material is acontinuous sheet of leaflet material. In another embodiment, thecontinuous sheet of leaflet material comprises an upper portion havingat least two arches extending upwardly therefrom. In another embodiment,the continuous sheet of leaflet material comprises one or more spacingsin the upper portion, wherein each of the one or more spacings isdisposed between two of the at least two arches. Moreover, the at leastone sheet of leaflet material comprises a polymer material that may belinear low density polyethylene, polytetrafluoroethylene, low-densitypolyethylene, polyethylene terephthalate, polypropylene, polyurethane,polycaprolactone, polydimethylsiloxane, polymethylmethacrylate,polyoxymethylene, thermoplastic polyurethane, and combinations thereof.The leaflet material may also include hyaluronic acid. And, the at leastone sheet of leaflet material may include a bioprosthetic material

In one embodiment, the stent frame has a height and an inner diameter,and wherein the ratio of height to diameter is from about 0.5 to about0.9. The at least two arches may have a height, and wherein the ratio ofthe height of the at least two arches to the inner diameter of the stentframe is from about 0.05 to about 0.12.

Finally, the at least one sheet of leaflet material has a threedimensional curvature and wherein the leaflet material is twodimensional when heated to form a rounded leaflet.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a front view of one embodiment of a prosthetic heart valve inan open position;

FIG. 2 is a perspective view of the prosthetic heart valve of FIG. 1;

FIG. 3 is a front view of one embodiment of a stent frame for use in aprosthetic heart valve;

FIG. 4 is a plan view of a rectangular pieces of leaflet material beforeit is attached to the stent frame;

FIG. 5 is a plan view of a piece of leaflet material including an archedupper edge;

FIG. 6 is a front view of one embodiment of a clip for use in aprosthetic heart valve;

FIG. 7 is an enlarged rear perspective view of one embodiment of the topportion of a clip for use in a prosthetic heart valve;

FIG. 8 is a front view of another embodiment of a stent clip and stentframe for use in a prosthetic heart valve;

FIG. 9 is a front view of another embodiment of a prosthetic heartvalve;

FIG. 10 is a perspective valve of the prosthetic heart valve of FIG. 8;

FIG. 11 is a front view of another embodiment of a stent frame for usein a prosthetic heart valve;

FIG. 12 is a perspective view of the stent frame of FIG. 11;

FIG. 13 is a front view of an alternative embodiment of a stent framefor use in a prosthetic heart valve;

FIG. 14 is a plan view of the stent frame of FIG. 13;

FIG. 15 is top view of the prosthetic heart valve of FIG. 13 with theleaflets in a closed position;

FIG. 16 is a plan view of a piece of leaflet material before it isattached to the stent frame of FIG. 13;

FIG. 17 is an exploded view of an alternative embodiment of a stentframe and an outer cover;

FIG. 18 is a front view of an alternative embodiment of a stent frame;

FIG. 19 is a front view of an alternative embodiment of a stent frame;

FIG. 20 is a perspective view of the stent frame of FIG. 19;

FIG. 21 is a front view of an alternative embodiment of a stent frame;

FIG. 22 is a perspective view of the stent frame valve of FIG. 21;

FIG. 23 is a front view of an alternative embodiment of a stent frame;

FIG. 24 is a perspective view of the stent frame of FIG. 23;

FIG. 25 is a front view of an alternative embodiment of a stent frame;

FIG. 26 is a perspective view of the stent frame of FIG. 25;

FIG. 27 is an exploded perspective view of an embodiment of a 3D printedmodel of a prosthetic heart valve;

FIG. 28 is a plan view of an embodiment of a 3D printed model of aprosthetic heart valve;

FIG. 29 is a graphical representation of a pressure and flow rates overtime for prosthetic heart valve Example 5 with a medium profile and ashort arch;

FIG. 30 is a graphical representation of the normalized flow rate overtime for prosthetic heart valve Examples 1-6;

FIGS. 31 and 32 are graphical representations of the reverse flowpercentages for the closing and regurgitation fractions of Examples 1-6;

FIGS. 33 and 34 are high speed camera images of Examples 1-6 taken atfour time point throughout a typical cardiac cycle;

FIGS. 35 and 36 are graphical representations of averages velocityvectors superimposed by vorticity contours and contours of normalizedReynolds shear stress at two time points throughout the cardiac cyclesfor Examples 1-6; and

FIGS. 37 and 38 are graphical depictions of hemodynamics for prostheticheart valves having a no arch and varying profiles and varying archheights, respectively.

DETAILED DESCRIPTION

A prosthetic heart valve (PHV), including a stent frame and leafletmaterial, having a tri-leaflet design for use to replace either afailing or damaged native aortic or mitral heart valve in a patient isprovided. Although we will refer to a tri-leaflet design, it should beapparent to one of skill in the art that any number of leaflets may becreated using the PHV described herein. In one embodiment, the PHV willprovide a prosthetic valve with a higher effective orifice compared toother prosthetic valves that are commercially available. The PHV willalso provide improved flow characteristics through the geometric designof both the stent frame and the leaflet.

In one embodiment, the design of the stent frame in combination with thedesign of the leaflets enable improved performance over othercommercially available prosthetic valves. For example, the design of theleaflet and/or the manner in which the leaflet is disposed on the stentframe may improve durability of the PHV, reduce the number of suturesrequired to assemble the PHV, and/or improve leaflet coaptation.

FIGS. 1 and 2 show illustrate a first embodiment of the PHV 10. In theembodiment, the PHV 10 includes a suture ring 12, a stent frame 14, aplurality of stent clips 16, and a sheet of leaflet material 32 whichmay be disposed between the stent frame 14 and the stent clips 16 inorder to form at least two leaflets 18.

In one embodiment the stent frame 14 may be formed of a single piece ofmaterial, however it should be recognized that multiple pieces of stentmaterial may be used to create a single stent frame 14. Referring now toFIG. 3, the stent frame 14 may be laser cut from a cylindrical tube orpipe. Alternatively, the stent frame 14 may be laser cut from a flatpiece of material, rolled into the desired shape, and affixed to holdthe shape at either of the free ends (not shown). In another embodiment,the stent frame may be “printed” or molded using additive manufacturingtechniques known to those of skill in the art.

Generally, the stent frame 14 includes a generally circular base 20defining the valve orifice of the PHV 10 and at least two, and in oneembodiment three, stent posts 22 extending upwardly from the base 20.The stent frame 14 may also include a plurality of suture openings 24 inorder to facilitate attachment of the stent frame 14 to the leafletmaterial 32 (as shown in FIG. 1).

The stent frame 14 may be made of stainless steel, nitinol, cobaltchromium or other suitable material. It should be understood that thebase 20 of the frame 14 may be generally circular in nature or it may beelliptical, oval, or other shape suitable to the curvature of thepatient's valve annulus. As shown in FIGS. 11 and 12, the base 20 mayalternatively have an undulating, rather than straight, shape to betterfit the anatomical curvature of a patient's vessel. It should also beunderstood that the stent posts 22 that extend from the base 20 of thestent frame 14 may be placed equidistant around the circumference of thestent frame 14 or they may be placed at irregular intervals in order tomore closely mimic the natural shape of the patient's native valve. Thestent frame 14 maybe be produced in varying sizes, depending on the sizeof the patient's heart. For example, the base 20 of the stent frame 14may have a diameter of 17, 19, 21, 23, 25, 27, 29, or 31 millimeters(mm). The base of the stent frame 14 may also include an additionalplurality of suture openings 26 intended to facilitate attachment of theframe 14 to the suture ring 12 (as shown in FIGS. 1 and 2).

The stent posts 22 generally extend upwards from the stent base 20. Inone embodiment, the stent posts 22 have a curved triangular shape,creating scalloped edges 28, extending between top point 30(a) and toppoint 30(b), top point 30(b) and top point 30(c), and top point 30(c)and top point 30(a). The stent posts 22, when wrapped with the leafletmaterial 32, define the leaflets 18 (or cusps) of the PHV 10, as shownin FIG. 1.

Referring now to FIGS. 1, 4, and 5, the leaflets 18 of the PHV 10 may becreated using a single piece of polymeric or bioprosthetic (such asporcine or bovine pericardium) material 32. It will also be understoodthat the leaflets 18 may also be created using separate pieces ofleaflet material affixed between each set of stent posts 22.

As shown in FIG. 4, in one embodiment, a continuous sheet of leafletmaterial 32 may include an upper edge portion 34 and be generallyrectangular in shape, or as shown in FIG. 5, may include an upper edgeportion 34 having at least one arch 36 extending upwardly therefrom.

The leaflet material 32 may be made of a polymeric material, such aslinear low density polyethylene (LLDPE), polytetrafluoroethylene (PTFE),low-density polyethylene (LDPE), polyethylene terephthalate (PET),polypropylene (PP), polyurethane, polycaprolactone (PCL),polydimethylsiloxane (PDMS), polymethylmethacrylate (PMMA),polyoxymethylene (POM), thermoplastic polyurethane (TPU), andcombinations thereof.

In one embodiment, the leaflet material 32 may be made of a polymericmaterial, such as LLDPE, that includes hyaluronic acid to prevent bloodclot and thrombosis formation. An example of this material is disclosedin U.S. application Ser. No. 14/381,332, entitled Glycosaminoglycan andSynthetic Polymer Material for Blood-Contacting Applications, which isincorporated herein by reference in its entirety.

As shown in FIG. 1, the leaflet material 32 may be wrapped about andsutured to the outer circumference of the stent frame 14 through theplurality of suture openings 24 in the stent posts 22, forming threeleaflets 18 resembling the tri-leaflet aortic heart valve in thenormally open position. It should be understood that a PHV may also bemade having two leaflets to mimic the bi-leaflet mitral heart valve.

By using a single continuous piece of leaflet material mounted aroundthe stent frame 14, the number of sutures required to assemble theleaflets 18 is reduced. However, it should be appreciated that multiplepieces of leaflet material 32 may be mounted about the outercircumference of the stent frame 14.

In one embodiment, the suture ring 12 may be covered in a suitablematerial, such as Dacron®, disposed atop the leaflet material 32, andaffixed to the stent frame 14 with sutures or other means, such as theuse of a suitable adhesive. By covering only the suture ring 12 withDacron® the outer and inner diameter of the PHV are reduced, allowingfor a larger valve area and, consequently, a higher effective orificearea.

Referring again to FIG. 1, once the leaflet material 32 is affixed tothe stent frame 14, stent clips 16 are affixed to each of the stentposts 22 through the suture openings or with adhesive, such that theleaflet material 32 is disposed there between. The stent clips 16 may beformed of stainless steel, nitinol, or other suitable material.

Referring specifically to FIGS. 6 and 7, in one embodiment, the stentclips 16 have a facial surface 38 and suture openings 40 that may belaser cut to mimic the shape of the outer surface of stent posts 22.Referring to FIG. 7, the stent clips 16 may also include a top pointportion 56 that includes a left flange 42, right flange 44, and topflange 46 that extend from the facial surface 38 of the stent clips 16toward the inner surface (not shown) of the stent frame 14.

In another embodiment, the outer surface of the stent clips 16 may becovered with Dacron® or other suitable material (not shown) in order toprovide smooth contact between the stent posts 22 and the vessel wall.

As shown in FIGS. 6 and 7, in one embodiment, the stent clips 16 may bedistinct pieces, formed separately from the stent frame 14. In anotherembodiment, as shown in FIG. 8, the stent clips 16 may be integrallyformed with the stent frame 14. In this embodiment, the top pointportion 56 of each stent clip 16 may be connected to the top pointportion 30 of the respective stent post 22. In this embodiment, thestent clips 16 can be folded at the connection point 58, with the facialsurface 38 of the stent clip 16 facing the outer surface of the stentpost 22. The stent clip 16 is then affixed to the stent posts 22 throughthe respective suture openings or with adhesive, sandwiching the leafletmaterial 32 there between, as described above.

As shown in FIG. 2, the stent clip flanges (42, 44, 46) are designed togather the leaflet material 32 at the stent post 22, enabling theleaflets 18 to mimic the function of a native aortic heart valve cusp,opening and closing with the flow of blood through the PHV 10.Specifically, the stent clips 16 provide improved commissure coaptationadjacent to the sent posts and enhance closing dynamics of the leaflets.

Referring to FIGS. 5, 9, and 10, in another embodiment, the leafletmaterial 32 may include an upper edge portion 34 with a plurality ofarches 36. It should be understood that the arches 36 may be formedintegrally with the single sheet of leaflet material 32 or may beattached to the upper edge portion 34 after the material is formed. Thearches 36 on the upper edge portion 34 provide arched leaflets 48 (asshown in FIG. 9), when wrapped around the stent frame 14. Through theuse of arched leaflets 48, it was discovered that flow reattachment isfacilitated and recirculation regions that are directly related tothrombus formation are decreased. In addition, the use of archedleaflets 48 provide an improved leaflet coaptation.

In another embodiment, once the sheet of leaflet material 32 isinstalled onto the stent frame 14, the leaflets 18 may be further formedby applying a combination of heat and pressure to the once the planarleaflets 18. This treatment can be used to further change the shape ofthe leaflets 18 into a three dimensional configuration (as is the casefor native valve leaflets). In one embodiment, vacuum pressure isapplied to the formed PHV 10 on the upstream side of the PHV to forcethe leaflets 18 to close and then heat is applied from the downstreamside in order to make the polymer (which is a thermoplastic) relax andstretch under the forces exerted by the vacuum. The resulting shape ofthe leaflets 18 may more closely resemble the patent's native leafletshape.

In other set of embodiments, the stent frame 14 may have various otherdesigns, while the leaflet material 32 may be secured to the stent frame14 in generally the same or similar manner as set forth above. In oneembodiment, as shown in FIGS. 11 and 12, the base 20 of the stent frame14 may have an undulating, rather than straight, shape to better fit theanatomical curvature of a patient's vessel.

In another embodiment, as shown in FIG. 17, an outer cap 166 may be usedto secure the leaflet material to the stent frame 114. In thisembodiment, the outer cap 166 may be disposed to fit over the outersurface of the stent frame 114, sandwiching the leaflet material betweenthe frame 114 and the cap 166.

In another set of embodiments, as shown in FIGS. 13-16, and 18-24, thePHV 10 may have a stent frame that includes an upper frame portion, abase, and at least two stent posts (e.g., two stent posts, three stentposts, etc.). Referring to FIG. 13 for example, the stent frame 114includes an upper frame portion or a first upper frame portion 160, abase 120, and stent posts 122 (e.g., at least two stent posts 122).Generally, the upper frame portion 160 has a shape that mimics that ofthe upper edge 162 of and between the stent posts 122. The upper frameportion 160 connects to the stent posts 122 only at each of the toppoints 130(a)-(c) by stent frame extensions 164(a)-(c), respectively.

In this embodiment, the leaflet material may be attached to the stentframe 114 as described above with the use of stent clips. However, in analternative embodiment, as shown in FIGS. 13, 14 and 15 the leafletmaterial may be attached to the stent frame 114 by weaving the singlepiece of leaflet material 132 between the stent frame 114 and the upperframe portion 160 such that either the bottom portion of the leafletmaterial (as shown in FIGS. 4 and 5) is disposed against the innersurface of the stent frame 114 and the upper portion of the leafletmaterial is disposed against the outside surface of the upper frameportion 160 or the bottom portion of the leaflet material is disposedagainst the outer surface of the stent frame 114 and the upper portionis disposed against the inner surface of the upper frame portion 160.The leaflet material may then be further secured to the stent frame 114using sutures or adhesives, as described above.

While reducing the number of sutures needed to secure the leafletmaterial to the frame 114, this embodiment also protects the formedleaflets (not shown) from possible tearing as they expand and contractover the top of the upper frame portion 160. Moreover, in embodimentsthat the leaflet material 132 is woven through the stent frame 114 asshown in FIGS. 13 and 15, the upper frame portion 160 gathers theleaflet material 132 and enables the leaflets 118 to mimic the functionof a native aortic heart valve cusp, opening and closing with the flowof blood through the PHV 10. As such, the stent clip may be eliminated.The leaflet material 132 may be further adhered to the outside of thestent frame 114 by using a minimal amount of sutures.

In another embodiment of the leaflet material, as shown in FIG. 16, thecontinuous sheet of leaflet material 132 may include one or morespacings or notches 137 in the upper edge portion 134. This embodimentof leaflet material is particularly useful with the stent frames shownand described in FIGS. 13-15. For example, each of the one or morespacing or notches 137 is between every two directly adjacent arches136. The one or more spacings 137 may improve coaptation of the leaflets118 when wrapped around stent frame extensions 164. For example, the oneor more spacing 137 may help accommodating the opening and closingmotions of the leaflets 118, such that the commissures 119 meet withbetter conformity to achieve better coaptation and ensure minimalreverse flow of the blood when the leaflets 118 are closed, as shown inFIG. 15.

As shown in FIGS. 18-20, the stent frame 114 may include multiple upperframe portions (as discussed in FIG. 13). For example, as shown in FIG.18, the stent frame 114 may include a first, second, and third upperframe portions 160, 168, and 170. Using the weaving technique describedabove, a single or multiple pieces of leaflet material may be applied tothe stent frame 114. For example, in one embodiment, three separatepieces of leaflet material may be applied to the stent frame 114 byincluding leaflet extensions that extend from the leaflet material bodyand may be woven through the various upper frame portions 160, 168, and170, in order to secure the leaflet material to the frame 114. Thistechnique may reduce the number of sutures needed to secure the materialto the frame.

As shown in FIGS. 21-26, in yet other embodiments, a stent frame 214 maybe made so that a minimal amount of stent material is needed. In thisembodiment, the leaflet material may be woven through the stent frame214 and an upper frame portion 260, as described above, however whenmultiple pieces of leaflet material are employed, the leaflet extensionsmay be disposed though slots 272 formed through the stent frame 214.

Referring now to FIGS. 25 and 26, like the stent frame 214 describedabove, a stent frame 314 is made of a minimal amount of material. Inthis embodiment, however, the stent frame 314 may be customized to fitindividual patients by varying the height of stent posts 322 and thedepth of a stent base 320.

The PHV may be implanted into a patient using known surgical techniques.However, it should be appreciated that modifications may be made to thePHV to enable implantation using known trans-catheter methods.

Examples

In order to assess the commissure coaptation and fluid dynamics of thePHV in the ascending aorta, six 3D printed models of the stent andcorresponding leaflets were produced to mimic the performance of thePHV. As shown in FIGS. 27 and 28, the models included a stent base 50, astent clip portion 52, and a sheet of LLDPE leaflet material 54 wrappedaround the stent base 50 and disposed between the base 50 and the stentclip portion 52. As shown in FIG. 28, the aspect ratio between stentheight and diameter (H/D) was varied for three different PHVs withratios listed in Table 1, below:

TABLE 1 Height (H) to Diameter (D) Aspect Ratio Low profile (LP) Mediumprofile (MP) High profile (HP) H/D 0.6 0.7 0.88

Also, the arch height to diameter aspect ratio, herby referred to ash/D, was varied as shown in Table 2, below:

TABLE 2 Parameters used to design leaflets No arch (NA) Short arch (SA)Long arch (LA) h/D 0 0.081 0.116

Those examples having configurations providing full commissurecoaptation were studied further, including models with a low profile/noarch (LPNA), low profile/short arch (LPSA), low profile/long arch(LPLA), medium profile/no arch (MPNA), medium profile/short arch (MPSA),and high profile/no arch (HPNA).

Examples 1-6 had a diameter of about 21.5 mm. The stent base 50 had acylindrical end, which serves to keep the leaflets in place and threestent posts to form the three cusps of the valve. The rectangular pieceof LLDPE 54 was cut and wrapped around the stent base 50, creating acylinder. The LLDPE 54 was fixed to the three stent posts to ensure asymmetric geometry in closed position of the leaflets. Fixing wasperformed by connecting the stent base 50 to an air vacuum and fixingthe LLDPE 54 by matching the three cusps.

In order to mimic the PHV 10, the stent clip portion 52 was placed ontop of the LLDPE 54 in a way that created three cusps resembling thetri-leaflet PHV in the normally closed position. The stent base 50 andthe stent clip portion 52 were secured together using three orthodonticrubber bands. FIG. 26 shows the assembling process for each of theExamples 1-6.

Flow Loop Setup

Each example valve was inserted into a transparent acrylic aorticchamber machined to mimic the outer walls of an aorta. The chamber wasthen placed in the aortic position of a left heart simulator that wascontrolled by an in-house LabVIEW program. The parameters of the leftheart simulator were adjusted to simulate the physiological flow andpressure conditions of the aortic valve in the in vitro setup, whichwere measured using ultrasonic flow probes (Transonic Inc., Ithaca,N.Y.), and the pressure upstream and downstream of the valve wasmeasured with Validyne pressure transducers (Validyne Engineering Corp.,Northridge, Calif.).

An ensemble average of flow curves was obtained over 20 cycles at anaverage resting condition (Heart Rate (HR)=60 bpm, Mean Aortic Pressure(MAP)=100 mmHg, Cardiac Output (CO)=5 L/min) using the aforementionedLabVIEW program. The working fluid for the flow loop was a mixture ofwater/glycerin with 38% glycerin concentration to produce a Newtonianblood analog of similar kinematic viscosity and density (ν=3.5 cSt,ρ=1080 kg/m³).

High Speed Imaging

The example valves' dynamic models were evaluated using high speedimaging and particle image velocimetry (NV). Both of these were doneusing the same aortic chamber, obtaining data from front viewing windowand lateral side. High speed videos were captured to analyze the overallperformance of the designed PHVs and to evaluate leaflet closure. To dothis, an acrylic dog-leg chamber was added to the downstream of aorticchamber and a high-speed CMOS camera (FASTCAM SA3, 60 kfps, 1024×1024px, Photron, Tokyo, Japan) was positioned in front of the dog-legwindow. Images were acquired at 1000 fps.

Particle Image Velocimetry

To visualize particle movement during the PIV process, the flow wasseeded with PMMA-Rhodamine B seeding particles (microParticles GmbH,Berlin, Germany) with particle sizes ranging from 1 to 20 μm. A lasersheet cut through the center plane of one leaflet and illuminated theparticles. The laser sheet was created using a Nd:YLF single-cavitydiode-pumped solid-state, high-repetition-rate laser (PhotonicIndustries, Bohemia, N.Y.) coupled with external spherical andcylindrical lenses and an orange filter. The high-speed camera wasplaced on the side of aortic chamber to view the laser sheet.Measurements were phase-locked with acquisition of 250 double-frameimages at each time point. Commercial PIV software, DaVis (LaVision,Germany), was used for data acquisition and processing.

Velocity vectors were calculated using an advanced PIV cross-correlationmethod with a 50% overlap multi-pass approach with an initialinterrogation window of 64×64 pixels which progressively reduced to 8×8pixels interrogation window passes. No pre-processing was done, butpost-processing was performed using a median filter that rejectedvectors outside 2 standard deviations of the neighbor vector. Theeffective spatial resolution was 27 μm/(pixel) and the temporalresolution was 1000 Hz. Particle seeding density was approximately 0.02particles per pixel and the particle displacement was around 0-10 pixelsper frame (average 5 pixels). The number of particles per interrogationwindow averaged 20.5 which are acceptable for high-quality PIV. Velocityvectors and vorticity contours were ensemble averaged across 5 trials.

Definition of the Calculated Parameters

The following parameters are used to characterize fluid dynamics in thevalve and the flow chamber used as model of the ascending aorta:

Regurgitation fraction: In order to make a comparison betweenregurgitant fractions that occur in each example valve, flow diagramsobtained from LabVIEW program assigned to the flow loop were analyzed.The regurgitation fraction is the ratio between reverse flow during thetime the valve is closed to the total flow in the loop. Leakagepercentage is defined as the ratio between the sum of the reverse flowsthat occur both during valve closure (closing fraction) and the durationof the time the valve is closed to the total flow in the loop(regurgitation fraction).

Effective Orifice Area (EOA): The effective orifice area (EOA) isanother parameter to evaluate valve's hemodynamic performance. EOA wascalculated using Gorlin equation, in which it is a function of both flowrate and transvalvular pressure gradient.

EOA=Q _(rms)/(51.6√(ΔP _(mean)))  (1)

Calculations were acquired over 10 cardiac cycles and then averaged toprovide the representative values in Table 3.

TABLE 3 Calculated values for the Effective Orifice Area and normalizedRSS of each valve model. LPNA LPSA LPLA MPNA MPSA HPNA EOA 2.57 ± 0.0871.99 ± 0.007 2.01 ± 0.415 2.74 ± 0.02 1.72 ± 0.031  1.89 ± 0.013Normalized 0.14 ± .008  0.023 ± 0.0029 0.016 ± 0.0014 0.040 ± 0.0050.017 ± 0.0001 0.029 ± 0.002 RSS

The coordinate system used to calculate different parameters are definedso that X direction is along the center plane of the heart valve andZ-direction is perpendicular to our interrogation window. U and V arevelocity components respectively along X and Y directions with u′ and v′as the velocity fluctuations in each direction.

Vorticity (ω_(z)): Regions of high vorticity indicate high tendency offluid elements swirling and rotating along one axis. Even though flowfield in aorta is three-dimensional, the vorticity along z-direction isdominant. 2D PIV results along X-Y plane provide vorticity field along Zaxis which is defined as follows:

ω_(z)=(∂V/∂x)−(∂U/∂y)  (2)

Principal Reynolds Shear Stress (RSS): It is known that high shearstress results in destruction of red blood cells (hemolysis). One methodto evaluate the performance of designed PHVs is to calculate RSS toobtain the optimal design for minimal blood damage. RSS is a componentof total shear stress calculated from Reynolds decomposition ofNavier-Stokes equation. RSS is defined as:

RSS=ρ√((((′u′)−( v′v′))/2)²+( u′v′) ²)  (3)

Turbulent Kinetic Energy (TKE): This parameter represents the kineticenergy per unit mass for eddies in a turbulent flow. The physiologicaleffect of high TKE is extended exposure of cells to high shear stressand will result in cell membrane rapture, platelet activation andthrombosis. For a 2D PIV, TKE is expressed as:

TKE=1/2( u′ ² + v′ ² )  (4)

Results

Hemodynamics Results

Pressure and flow data were acquired for all six examples from LabVIEW.As shown in FIG. 29, the pressure and flow curve for the MPSA PHV wasplotted (series 401 corresponds an aortic pressure cure, series 402corresponds to a ventricular pressure curve, and series 403 correspondsto a flow rate curve). The flow loop was adjusted to match physiologicalconditions and the pressure curves for the four valves, except the LPNA,were found to have the same general shape.

However, the LPNA valve failed to maintain the desired 120/80 mm Hgpressures. Flow was normalized by the maximum flow rate for each valvemodel and the normalized flow curves for all six valves are presented inFIG. 30. The comparison between flow curves obtained for each valveindicates an improvement in commissure coaptation based on the reductionin back flow as profile length increased or when leaflet arches wereadded. The regurgitation fraction is further quantified for both H/D andh/D aspect ratios. FIGS. 31 and 32 show a decrease in regurgitationfraction with the increment in H/D and h/D respectively. The error barsin FIGS. 31 and 32 represent the calculated standard deviation for eachvalue.

Leaflet Kinematics

Coaptation kinematics were further studied using high-speed cameraimages of each valve in the flow loop. Images were acquired during fourtime points throughout the cardiac cycle: Early Systole (ES), PeakSystole (PS), Late Systole (LS) and Diastole. The first set ofexperiments were carried out using the three valve model exampleswithout arches to evaluate the effect of H/D (FIG. 33). The second setwere for the medium and short profile valves with short and long archadded to their leaflets to study the effect of h/D (FIG. 34). Asobserved in FIGS. 33 and 34, the large gap at the center of commissuresin the LPNA valve is diminished as either the stent profile or the archlength increase. This observation indicates the increment in commissuralcontact as the aspect ratio and arch height increase.

The LPLA valve in FIG. 34 shows warping of commissures at diastole andsmall amount of asymmetry at PS. FIG. 33 also indicates that obtaining asymmetrical leaflet opening is easier when the leaflets have no archadded. MPSA had an asymmetric leaflet opening with a lag time for oneleaflet to open all the way which can result in undesired fluid motionduring early systolic phase.

Quantitative Flow Results

High resolution PIV was used to capture turbulent characteristicsthrough the aortic valve and ascending aorta. Ensemble averaged velocityvectors superimposed by vorticity contours are shown at two time points(ES and PS) throughout the cardiac cycle for each PHV in the left panelsof FIG. 35 and FIG. 36 to show the effect of stent height and leafletarch respectively. As illustrated, the averaged velocity vectors for thesix example PHVs are plotted based on the scale bar representingvorticity in a unit of inverse seconds (s⁻¹). At early systole (ES) theexamples with an arch result in an asymmetric velocity profile skewedtoward the top along the centerline of the chamber. No significantdifference was observed in the values for velocity for each example. Themaximum velocity during ES was ranged from 1.3 m/s for MPNA to 1.8 m/sfor LPLA. The flow streamlines for LPLA and MPSA were curved, showing adownward motion towards lower part of the flow chamber and then upwardmotion to obtain a straight streamline through the rest of themeasurement plane.

The central orifice jet in short profile valves initiated perfectlysymmetric during ES, however during PS the central jet for LPNA showedan upward motion at the trailing edge of the leaflet and resulted inlarger separation region in the lower portion of the chamber. Except forLPSA, the other PHVs produced separation zone only on the lower part ofthe flow chamber, corresponding to the side of the valve with the stentpost, as opposed to a free leaflet edge. No reattachment point wasobserved for the HPNA PHV in the measurement plane; while the rest ofthe PHVs showed reattachment points in 1-2 diameters downstream of theannulus (e.g., the distance from the annulus to the reattachment pointis between 1 to 2 times the diameter of the respective valve size), asobserved in FIGS. 37 and 38. Maximum velocity during PS is assigned toLPNA and was measured 3.1 m/s.

Maximum peak velocity for the other PHVs ranged between 1.8 m/s to 2.2m/s. The velocities downstream of the trailing edge of the leafletduring diastole were typically less than 0.1 m/s for all the examplesexcept for LPNA and MPNA which were measured 0.35 m/s and 0.17respectively. The reason for higher diastolic velocity in these two PHVswas the presence of a leakage jet at the center of the commissuralregion. The velocity for this leakage jet was 0.7 m/s and 0.2 m/s forLPNA and MPNA models respectively.

RSS and TKE Distribution

Reynolds shear stress (RSS) is a critical parameter in predicting blooddamage and calcification in heart valves. Contours of normalized RSSnear PHV leaflets and inside the ascending aorta are provided in theright panels in FIGS. 35 and 36, for varying stent profile and archlength to study the propensity of blood cell damage in each of the sixexamples. Normalized values were calculated to take the difference inpeak velocity for each example into account. As illustrated, thenormalized RSS for the six PHVs are plotted based on the scale barrepresenting RSS (e.g., a unitless number). The highest value for RSS isobserved in the LPNA during PS, which is 1940 dyne/cm2 with normalizedRSS value of 0.14±0.008. Adding leaflet arches as well as increasingaspect ratio decreased RSS one order of magnitude. However, MPNA showedhigher normalized RSS values in comparison to the other four valve, andwas measured to be 0.04±0.004. The LPLA valve configuration resulted inthe smallest value of normalized RSS, which was 0.016±0.0014. Themeasured valued for normalized RSS is presented in Table 3, above.Generally high regions of RSS were observed in the shear layer regionbetween the central orifice jet and at the trailing edge of theleaflets. As shown in FIGS. 35 and 36, regions of high RSS values werediminished when arches were added to the leaflets.

Contours of TKE bear a resemblance to RSS plots shown in FIGS. 35 and36. LPNA had highest magnitudes of TKE, corresponding to higher levelsof kinetic energy for turbulent eddies. Similar to RSS, TKE was alsodecreased with the addition of leaflet arches and increment in aspectratio.

Discussion Effect of Heart Valve Profile Hemodynamics and Kinematics ofLeaflets

One major parameter that needs to be taken into account for the AVhemodynamics is to ensure a negligible regurgitation fraction duringdiastole to minimize the work of the heart and avoid a high shear stressjet that can induce platelet activation and hemolysis. Appropriatesealing of the leaflets is obtained through a proper aspect ratio or amodified leaflet design. Generally, short profile heart valves are moredesirable due to the reduced dead space by diminishing the blockage ofcoronary ostium and aortic sinuses. The dead space created in higherprofile PHVs supports coagulation and will increase the risk forthromboembolic complications.

The high-speed camera snapshots shown in FIG. 33 indicate that theaspect ratio of LPNA and MPNA models was not large enough to cover thecentral gap, which leads to flow regurgitation throughout diastole. Theregurgitant flow in these two valve models can be detected in thediastolic phase of the cardiac cycle.

All designed models were able to withstand the physiological flow andpressure condition except for the LPNA model which showed higherpressure drops across the PHV during systolic phase. This is due to theincrement in the peak flow rate to maintain an average flow ratecompensating for regurgitation.

Based on the EOA values provided in Table 3, the highest value for EOAwas achieved in the MPNA valve. A decrement in EOA was observed in theHPNA valve, which is likely due to the fact that the larger leafletstake more time to fully open. The EOA for LPNA valve is shown to berelatively high, and this is likely due to the fact that LPNA valveconfiguration was not able to withstand normal pressure gradient of80-120 mmHg.

Velocity and Vorticity Results

The Velocity and vorticity pattern observed in the center orifice jetshows a great dependence to the PHV geometry. LPNA and MPNA modelscreated jets with higher systolic peak velocity throughout the ascendingaorta. The higher downstream velocity present in these models is tocompensate for the regurgitating flow during diastole and keep theaverage flow rate at the desired value of 5 L/s. No reattachment pointswere observed for the lower part of the HPNA model in our view plane.The reason for delayed reattachment appears to be the presence of longerstent posts act as a barrier and create a larger turbulent shear zonewhich delays reattachment (FIG. 37). This implies leaflet coaptationdoes not necessarily correlate to an optimum PHV geometry.

Comparing all three examples together shows that the central orifice jetfor the MPNA valve models achieved unidirectional flow sooner than theother two models by creating reattachment points in the 1D downstream ofthe trailing edge of the leaflets.

Effect of RSS and TKE

High values of RSS are strongly correlated to hemolysis and blooddamage. The RSS values reduced dramatically as a result of an enhancedleaflet coaptation. The high values of RSS and TKE were more dominantlyobserved in the LPNA and MPNA valve models, which shows the contributionof the leakage jet in increasing the risk of blood damage. The HPNAmodel also resulted in larger values of RSS and TKE throughout theascending aorta. The values measured for RSS in these examples is wellbelow the results found previously, however they still are above thereported values for RSS threshold (˜400 dyne/cm²) suggested by previousstudies which can cause hemolysis and platelet activation.

Effect of Leaflet Arch Leaflet Kinematics

The results indicate that leaflet arch dramatically improves commissurecoaptation. The leakage flow percentage reduced from 150% in the LPNAmodel to 5.6% in the LPLA configuration. As a result the maximum PSdownstream velocity reduced to 58% of its value in LPNA to 1.8 m/s inLPSA valve model. Additionally, maximum RSS value reduced 40% from theLPNA to LPLA model. Increments in leaflet arch length resulted inwarping in the leaflet tips during diastole, which can increase thechance of fatigue. Warping was observed in the LPLA and became morenoticeable for the MPSA, which also resulted in reduced EOA. Anasymmetric leaflet opening and closing seen for MPSA example (FIG. 34)is associated with the warping of the leaflets in their closed position.Long leaflet arches resulted in one leaflet being pushed underneath theother two which is another reason of the asymmetric opening and closingof the MPSA example.

Additionally, the EOA value for the MPSA is lower than LPSA and LPLA andthis can be due to the larger size of leaflets and the lag in theopening time compared to the other two.

Velocity and Vorticity Results

FIG. 37 shows jets of fluid through PHVs with different stent profiles(e.g., low profile, medium profile, high profile) and FIG. 38 shows jetsof fluid through PHVs with different leaflet arch (e.g., no arch, arch).In FIG. 37, the blue, red, and green profiles correspond to jets offluid for the LPNA, MPNA, and HPNA models, respectively. In FIG. 38, theblue and red profiles correspond to jets of fluid for the LPNA and LPSAmodels, respectively. In both figures the black arrows indicate wherereattachment points to the aortic wall occur for the respective valvedesign. Earlier reattachment points were observed in both top and bottomsections of the ascending aorta for LPLA and MPNA models. The flexiblearches may create a wider opening for the jet of fluid exiting throughthe PHV. As shown in the schematic drawing in FIG. 37, due to Coandaeffect the fluid jet stays attached to the arch surface and thisattachment deviates flow from the straight path guiding the flow to ahigher point in the sinus area. Moreover, increasing the exit diameteras the starting flow develops results in higher-energy vortex ringstructures with peak vorticity located further from the axis of symmetryrelative to a static nozzle case. The flexible arches facilitatetransfer of impulse to a greater volume of fluid and result in anenhanced turbulent mixing as well as helping the flow to slow down. Thisreveals the critical role that leaflet arches play in damping velocityfluctuations and initiates sooner reattachment. Hence, reduces theresidence time in recirculation zones and decreases the chance ofplatelet activation and blood damage.

Even though arches provided earlier reattachment to the ascending aorta,the added arch increases leaflet area, requiring more pressure to openthe leaflet all the way. The delayed opening of flaps during earlysystolic pushes the fluid towards the center of the chamber, resultingin vortex rings in the trailing edge of the leaflets (FIG. 36). ViscousShear Stress (VSS) data presents much lower values for all six valvemodels in comparison to mechanical heart valves, indicating a much lowerblood damage potential.

Effect of RSS and TKE

The RSS values reduced dramatically, since the reduced leakageassociated with coaptation resulted in reduced peak flow to maintain anaverage cardiac output. Additionally, the presence of arches at leaflettips could act as damping mechanism by providing a variable exitdiameter for the orifice jet and reduce RSS and TKE values.

Combined Effects and Interactions

Comparison of coaptation in MPNA and LPSA indicates commissural contactis more easily accomplished by the addition of leaflet arches. Thecombination of leaflet arch and increased profile height observed inMPSA design led to better overall hemodynamic performance. This is dueto the fact that longer arches increase asymmetric leaflet opening dueto warping; therefor, making short arches preferable.

Generally, it was demonstrated that leaflet arches and higher heartvalve profile provide several advantages such as: 1) resulting in adramatic decrease in the RSS, 2) yielding to better leaflet coaptation,and 3) minimizing regurgitation percentage. However, high stent profilemay delay reattachment of flow in the aorta and slightly increases RSS.This increment can potentially escalate hemolysis and blood damage.Leaflet arches result in great enhancement of leaflet kinematics and PHVhemodynamics by optimizing the low profile design of the heart valve.

To the extent that the term “includes” or “including” is used in thespecification or the claims, it is intended to be inclusive in a mannersimilar to the term “comprising” as that term is interpreted whenemployed as a transitional word in a claim. Furthermore, to the extentthat the term “or” is employed (e.g., A or B) it is intended to mean “Aor B or both.” When the applicants intend to indicate “only A or B butnot both” then the term “only A or B but not both” will be employed.Thus, use of the term “or” herein is the inclusive, and not theexclusive use. See Bryan A. Garner, A Dictionary of Modern Legal Usage624 (2d. Ed. 1995). Also, to the extent that the terms “in” or “into”are used in the specification or the claims, it is intended toadditionally mean “on” or “onto.” To the extent that the term“substantially” is used in the specification or the claims, it isintended to take into consideration the degree of precision available orprudent in manufacturing. To the extent that the term “operablyconnected” is used in the specification or the claims, it is intended tomean that the identified components are connected in a way to perform adesignated function. As used in the specification and the claims, thesingular forms “a,” “an,” and “the” include the plural. Finally, wherethe term “about” is used in conjunction with a number, it is intended toinclude ±10% of the number. In other words, “about 10” may mean from 9to 11.

As stated above, while the present application has been illustrated bythe description of embodiments thereof, and while the embodiments havebeen described in considerable detail, it is not the intention of theapplicants to restrict or in any way limit the scope of the appendedclaims to such detail. Additional advantages and modifications willreadily appear to those skilled in the art, having the benefit of thepresent application. Therefore, the application, in its broader aspects,is not limited to the specific details, illustrative examples shown, orany apparatus referred to. Departures may be made from such details,examples, and apparatuses without departing from the spirit or scope ofthe general inventive concept.

1. A prosthetic heart valve comprising: a stent frame comprising a firstupper frame portion, a base, and at least two stent posts extendingupwardly from the base; wherein the base is connected to the first upperframe portion by the at least two stent posts, and wherein the firstupper frame portion, the base, and the at least two stent posts each hasan inner surface and an outer surface; and at least one sheet of leafletmaterial configured to weave through the stent frame from the outersurface to the inner surface between the first upper frame portion andthe base of the stent frame.
 2. The prosthetic heart valve of claim 1,wherein the at least one sheet of leaflet material is disposed on theouter surface of the base and of the at least two stent posts, and atleast a portion of the at least one sheet of leaflet material is tuckedunder the first upper frame portion between the first upper frameportion and the base and is disposed on the inner surface of the upperframe portion.
 3. The prosthetic heart valve of claim 1, wherein the atleast one sheet of leaflet material is disposed on the inner surface ofthe base and of the at least two stent posts, and at least a portion ofthe at least one sheet of leaflet material is tucked in under the firstupper frame portion between the first upper frame portion and the base.4. The prosthetic heart valve of claim 1, wherein the first upper frameportion has a shape that is substantially similar to an upper edge ofthe base.
 5. The prosthetic heart valve of claim 1, comprising a secondupper frame portion connected to the first upper frame portion, and thesecond upper frame portion has a shape that is substantially similar toan upper edge of the first upper frame portion.
 6. The prosthetic heartvalve of claim 5, comprising a third upper frame portion connected tothe second upper frame portion, and the third upper frame portion has ashape that is substantially similar to an upper edge of the second upperframe portion.
 7. The prosthetic heart valve of claim 6, wherein the atleast one sheet of leaflet material weaves through the stent framebetween the first upper frame portion and the second upper frame portionand/or between the second upper frame portion and the third upper frameportion.
 8. The prosthetic heart valve of claim 1, wherein the base hasan lower edge that is substantially similar to a lower edge of the firstupper frame portion.
 9. The prosthetic heart valve of claim 1, whereinthe at least two stent posts have at least two heights different fromone another.
 10. The prosthetic heart valve of claim 1, wherein the atleast one sheet of leaflet material is a continuous sheet of leafletmaterial.
 11. The prosthetic heart valve of claim 10, wherein thecontinuous sheet of leaflet material comprises an upper portion havingat least two arches extending upwardly therefrom.
 12. The prostheticheart valve of claim 11, wherein the continuous sheet of leafletmaterial comprises one or more spacings in the upper portion, whereineach of the one or more spacings is disposed between two of the at leasttwo arches.
 13. The prosthetic heart valve of claim 1, wherein the atleast one sheet of leaflet material comprises a polymer material. 14.The prosthetic heart valve of claim 13, wherein polymer materialcomprises linear low density polyethylene, polytetrafluoroethylene,low-density polyethylene, polyethylene terephthalate, polypropylene,polyurethane, polycaprolactone, polydimethylsiloxane,polymethylmethacrylate, polyoxymethylene, thermoplastic polyurethane,and combinations thereof.
 15. The prosthetic heart valve of claim 14,wherein the polymer material is linear low density polyethylene.
 16. Theprosthetic heart valve of claim 13, wherein the at least one sheet ofleaflet material further comprises hyaluronic acid.
 17. The prostheticheart valve of claim 1, wherein the stent frame has a height and aninner diameter, and wherein the ratio of height to diameter is fromabout 0.5 to about 0.9.
 18. The prosthetic heart valve of claim 17,wherein the at least two arches have a height, and wherein the ratio ofthe height of the at least two arches to the inner diameter of the stentframe is from about 0.05 to about 0.12.
 19. The prosthetic heart valveof claim 1, wherein the at least one sheet of leaflet material comprisesa bioprosthetic material.
 20. The prosthetic heart valve of claim 1,wherein the at least one sheet of leaflet material has a threedimensional curvature and wherein the leaflet material is twodimensional.